Serum Deprivation-Induced Human GM3 Synthase (hST3Gal V) Gene Expression Is Mediated by Runx2 in Human Osteoblastic MG-63 Cells
Overview
Chemistry
Molecular Biology
Authors
Affiliations
Serum deprivation (SD) is well known to induce G0/G1 cell cycle arrest and apoptosis in various cells. In the present study, we firstly found that SD could induce G1 arrest and the differentiation of human osteoblastic MG-63 cells, as evidenced by the increase of osteoblastic differentiation markers, such as bone morphogenetic protein-2 (BMP-2), osteocalcin and runt-related transcription factor 2 (Runx2). In parallel, gene expression of human GM3 synthase (hST3Gal V) catalyzing ganglioside GM3 biosynthesis was upregulated by SD in MG-63 cells. The 5'-flanking region of the hST3Gal V gene was functionally characterized to elucidate transcriptional regulation of hST3Gal V in SD-induced MG-63 cells. Promoter analysis using 5'-deletion constructs of the hST3Gal V gene demonstrated that the -432 to -177 region functions as the SD-inducible promoter. Site-directed mutagenesis revealed that the Runx2 binding sites located side-by-side at positions -232 and -222 are essential for the SD-induced expression of hST3Gal V in MG-63 cells. In addition, the chromatin immunoprecipitation assay also showed that Runx2 specifically binds to the hST3Gal V promoter region containing Runx2 binding sites. These results suggest that SD triggers upregulation of hST3Gal V gene expression through Runx2 activation by BMP signaling in MG-63 cells.
An S, Yoon H, Kim K, Kim H, Cho J, Kim H PLoS One. 2023; 18(11):e0293321.
PMID: 37917776 PMC: 10621931. DOI: 10.1371/journal.pone.0293321.
Deficiency of GD3 Synthase in Mice Resulting in the Attenuation of Bone Loss with Aging.
Yo S, Hamamura K, Mishima Y, Hamajima K, Mori H, Furukawa K Int J Mol Sci. 2019; 20(11).
PMID: 31185614 PMC: 6600367. DOI: 10.3390/ijms20112825.
Lee M, Choi H, Kim K, Kim D, Kim C, Lee Y Evid Based Complement Alternat Med. 2018; 2018:6746412.
PMID: 30534177 PMC: 6252237. DOI: 10.1155/2018/6746412.
Zhang M, Cai X, Jing K, Pi X, Liao P, Li S Biomed Res Int. 2018; 2018:7174561.
PMID: 29850553 PMC: 5907408. DOI: 10.1155/2018/7174561.
Yoon H, An H, Ko M, Kim K, Mun S, Kim D Int J Mol Sci. 2016; 17(8).
PMID: 27490539 PMC: 5000644. DOI: 10.3390/ijms17081246.